CBD User's Manual

A Beginner's Guide to Cannabidiol & Cannabis Therapeutics
CBD User's Manual: A Beginner's Guide to Cannabis Therapeutics
By on July 13, 2016

In 2009, a handful of CBD-rich cannabis strains were discovered serendipitously in Northern California, America’s cannabis breadbasket, where certified patients could access medical marijuana legally. Thus began a great laboratory experiment in democracy involving CBD-rich cannabis therapeutics. The advent of whole plant CBD-rich oil as a grassroots therapeutic option has changed the national conversation about cannabis. It’s no longer a question of whether medical marijuana works – today the key question is how to use cannabis for maximum therapeutic benefit. But most health professionals have little experience in this area. So Project CBD has created a CBD User’s Manual for patients that addresses key questions about cannabidiol and cannabis therapeutics.

What is CBD?

Cannabidiol or CBD is a non-intoxicating component of the cannabis plant with enormous therapeutic potential. Although CBD doesn’t make people feel high like THC does, it’s causing quite a buzz among scientists, health professionals, and medical marijuana patients who are using CBD-rich products to treat a wide range of conditions - chronic pain, cancer, Crohn’s, diabetes, rheumatoid arthritis, PTSD, cardiovascular disease, anxiety, antibiotic-resistant infections, multiple sclerosis, schizophrenia, and more. Academic research centers in the United States and elsewhere are currently studying the effects of CBD on these and other ailments. Scientists refer to CBD as a “promiscuous” compound because it confers therapeutic benefits in many different ways while tapping into how we function physiologically and biologically on a deep level. Extensive preclinical research and some clinical studies have shown that CBD has strong anti-oxidant, anti-inflammatory, anticonvulsant, anti-depressant, anti-psychotic, anti-tumoral, and neuroprotective qualities. Cannabidiol can change gene expression and remove beta amyloid plaque, the hallmark of Alzheimer’s, from brain cells.

Which is better CBD or THC? Cannabidiol and THC (The High Causer) are the power couple of cannabis therapeutics; they work best together. CBD and THC interact synergistically to potentiate each other’s curative qualities. CBD enhances THC’s painkilling and anticancer properties, while lessening THC’s psychoactivity. CBD can also mitigate adverse effects caused by too much THC, such as anxiety and rapid heartbeat. When both compounds are present in sufficient amounts in the same cannabis strain or product, CBD will lower the ceiling on the THC high while prolonging its duration. (“Relaxing but not intoxicating” is how one patient described CBD-rich cannabis.) CBD broadens the range of conditions treatable with cannabis, such as liver, cardiovascular and metabolic disorders, which may be less responsive to THC-dominant remedies. CBD and THC both stimulate neurogenesis, the creation of new brain cells, in adult mammals.

What’s the best way to take CBD? The most appropriate delivery system for CBD-rich cannabis is one that provides an optimal dose for a desired duration with few unwanted side effects. CBD-rich cannabis flower varietals for smoking or vaping are available in many medical marijuana dispensaries, but most CBD patients prefer non-inhalable products made with cannabis oil concentrates. Although banned by federal law, measurable doses of potent CBD-rich cannabis remedies are available in many non-smokable forms and can be utilized in various ways. The time of onset and duration of effect vary depending on the method of administration. CBD-rich cannabis oil products can be taken sublingually, orally (as edibles, lozenges, beverages, tinctures, and gel caps), or applied topically. Concentrated cannabis oil extracts can also be heated and inhaled with a vape pen. Inhalation is good for treating acute symptoms that require immediate attention; the effects can be felt within a minute or two and typically last for a couple of hours. The effects of orally administered CBD-rich cannabis oil can last for four hours or more, but the onset of effects is much slower (30-90 minutes) than inhalation.

Read more: Different Types of Cannabis Medicine

Can CBD cure epilepsy? Marijuana has a rich history as a medicine for quelling seizures and convulsions going back thousands of years. In the mid-19th century, the U.S. Pharmacopeia listed cannabis tincture as a treatment for pediatric epilepsy, and subsequent scientific studies have documented the anticonvulsant effects of CBD, THC, and whole plant cannabis. CBD-dominant/low- THC cannabis strains and oil extracts can facilitate dramatic improvement in some children with intractable seizure disorders. Between 10-15 percent of severe childhood epileptics who are given CBD oil products experience a near complete cessation of seizures; most improve (with a decrease but not total elimination of seizures); and some children have worse seizures when they take CBD. Many parents of epileptic children have learned through trial and error that augmenting CBD-rich oil by adding some THC -- or better yet, THCA, the unheated, non-psychoactive form of THC that’s present in raw cannabis flowers and leaves -- helps with seizure control. The take-home message: Low-THC cannabis oil products don’t work for everyone. Patients of all ages need access to a wide spectrum of whole plant cannabis remedies, not just high CBD oil.

Read more: List of studies on CBD & epilepsy

What is the right CBD:THC ratio for me? Cannabis therapeutics is personalized medicine. There is no single ratio or strain or product that’s right for everyone. Optimize your therapeutic use of cannabis by finding the proper combination of CBD and THC that works best for you. A person’s sensitivity to THC is a key factor in determining the appropriate ratio and dosage of CBD-rich medicine. Many people enjoy the cannabis high and can consume reasonable amounts of any cannabis product without feeling too high or dysphoric. Others find THC unpleasant. CBD can lessen or neutralize the intoxicating effects of THC. So a greater ratio of CBD-to- THC means less of a high. In some states with medical marijuana laws, cannabis oil concentrates and other products with varying ratios of CBD:THC are available so users can adjust or minimize psychoactive effects to suit their needs and sensitivities. Those who don’t like THC have the option of healing without the high by using a CBD-rich remedy with only a small amount of THC. But a low THC remedy, while not intoxicating, is not always the most effective treatment option. In essence, the goal is to administer consistent, measurable doses of a CBD-rich remedy that includes as much THC as a person is comfortable with.

Are specific CBD:THC ratios better for different conditions? Some patterns are beginning to emerge. For anxiety, depression, spasms, psychosis, and seizure disorders, many people report they do well starting with a small dose of a CBD-rich remedy with little THC. For cancer, autism, and many other diseases, some say they benefit more from a balanced ratio of CBD and THC. Extensive clinical trials conducted outside the United States have shown that a 1:1 CBD:THC ratio can be effective for neuropathic pain. Some people use cannabis products with different CBD:THC ratios at different times of the day (more CBD for sunlight hours, more THC at night). Almost any cannabis strain or product theoretically could benefit a wide range of autoimmune and inflammatory disorders because THC and other cannabis components activate the CB2 cannabinoid receptor, which regulates immune function. Note: The CBD:THC ratio in not an indication of how much CBD or THC is present in a given cannabis product or strain.

What is the optimal dosage of CBD? An effective dosage can range from as little as a few milligrams of CBD-enriched cannabis oil to a gram or more. Begin with a small dose of high CBD/low THC oil, especially if you have little or no experience with cannabis. Take a few small doses over the course of the day rather than one big dose. Use the same dose and ratio for several days. Observe the effects and if necessary adjust the ratio or amount. Don’t overdo it. Cannabis compounds have biphasic properties, which means that low and high doses of the same substance can produce opposite effects. Small doses of cannabis tend to stimulate; large doses sedate. Too much THC, while not lethal, can amplify anxiety and mood disorders. CBD has no known adverse side effects, but an excessive amount of CBD could be less effective therapeutically than a moderate dose. “Less is more” is often the case with respect to cannabis therapy. 

Read more: Cannabis Dosing Guide

What should one look for when choosing a CBD-rich product? Look for products with clear labels showing the quantity and ratio of CBD and THC per dose, a manufacturing date, and a batch number (for quality control). Select products with quality ingredients: No corn syrup, transfats, GMOs, artificial additives, thinning agents or preservatives. CBD-rich products should be lab tested for consistency and verified as being free of mold, bacteria, pesticides, solvent residues, and other contaminants. Best to avoid products extracted with toxic solvents like BHO, propane, hexane or other hydrocarbons. Opt for products that utilize safer extraction methods such as supercritical CO2 or food-grade ethanol.

Read more: What To Look For In Your Cannabis Medicine

If CBD is so good, won’t pure CBD be even better? Single-molecule CBD will inevitably become a federally approved Big Pharma medicine. Products infused with a crystalline CBD isolate, derived and extensively refined from industrial hemp, are already being marketed by unregulated internet storefronts. But single-molecule CBD is less effective therapeutically than whole plant CBD-rich oil extract. Scientific studies have established that synthetic, single-molecule CBD has a very narrow therapeutic window and requires precise, high doses for efficacy, whereas lower dose, whole-plant, CBD-rich treatment regimens are already showing efficacy for many conditions among patients in medical marijuana states. Whether synthesized in a Big Pharma lab or derived from industrial hemp, single-molecule CBD lacks critical secondary cannabinoids and other medicinal compounds found in high-resin cannabis strains. These compounds interact with CBD and THC to enhance their therapeutic benefits. Scientists call this the “entourage effect.” Numerous cannabis compounds have medicinal attributes, but the therapeutic impact of whole plant cannabis is greater than the sum of its parts.

Read more: Synthetic vs. Whole Plant CBD

Is there a difference between CBD derived from hemp and CBD derived from marijuana? If you live in a state where medical marijuana is legal and available, look for CBD products made from high-resin cannabis (rather than low resin industrial hemp) that are sold in medical marijuana dispensaries. Hemp-derived CBD-infused products of varying quality are also available via dozens of internet storefronts. Compared to whole plant CBD-rich cannabis, industrial hemp is typically low in cannabinoid content. A huge amount of hemp is required to extract a small amount of CBD, thereby raising the risk of contaminants because hemp, a bioaccumulator, draws toxins from the soil. That’s a great feature for restoring a poisoned ecosystem, but it’s not recommended for extracting medicinal oil. Heavily refined CBD paste or terpene-free CBD powder is poor starter material for formulating CBD-rich oil products. The FDA has tested dozens of so-called CBD “hemp oil” products and found that in many cases these products contained little or no CBD. CBD-infused nutraceuticals have not been approved by the FDA as food supplements; nor are these products legal in all 50 U.S. states. By and large, however, interstate CBD commerce is tolerated by federal authorities.

Read more: Sourcing CBD: Marijuana, Industrial Hemp & the Vagaries of Federal Law

Is it safe to inhale hemp CBD oil fumes from a vape pen? Many cannabis- and hemp-derived CBD vape oil products include a thinning agent, which dilutes the oil that is heated and inhaled by vape pen users. Beware of vape pen oil that contains propylene glycol. When overheated, this chemical additive produces formaldehyde, a carcinogen, as a byproduct, according to a 2015 report in the New England Journal of Medicine. Why do so many vape oil products contain this thinning agent? It’s because of the dubious quality of the extracted material from which these unregulated cannabis oil products are made.

Read more: How Safe is Your Vape Pen?

Does CBD have any adverse side effects? What about drug interactions? CBD is a very safe substance, but patients taking other medications should check with their doctor about drug interactions, which are more likely when consuming high doses of single-molecule CBD products. At sufficient dosages, CBD will temporarily deactivate cytochrome P450 enzymes, thereby altering how we metabolize a wide range of compounds, including THC. Cytochrome P450 enzymes metabolize more than 60 percent of Big Pharma meds. CBD is a more potent inhibitor of cytochrome P450 than the grapefruit compound Bergapten, so ask your doctor if grapefruit interacts with your medication. If grapefruit does, then CBD probably does, too. Patients on a CBD-rich treatment regimen should monitor changes in blood levels of prescription medications and, if need be, adjust dosage.

Read more: CBD-Drug Interactions: Role of Cytochrome P450

Will big pharmaceutical companies control the CBD market when cannabis is legalized for adult use? Only if we let them. Cannabis is a medicinal herb and it should be regulated as an herb, not as a pharmaceutical or a street drug.

Copyright, Project CBD. May not be reprinted without permission.

Is CBD Really Non-Psychoactive?

cb1 receptor cbd non-psychoactive
By on May 17, 2016


Understanding how cannabidiol (CBD) exerts its myriad effects on human physiology is a work in progress. Thus far, scientists have identified more than 60 different molecular pathways through which CBD operates. It is known, for example, that CBD acts through multiple receptor-independent channels and it also binds to various receptors in the brain, including serotonin 5HT1A (which contributes to CBD’s antidepressant effect), TRPV1 (which contributes to CBD’s anti-psychotic effect), the nuclear receptor PPAR-gamma (regulates gene expression), and the orphan receptor GPR55, among others.

CBD and tetrahydrocannabinol (THC) have similar molecular structures, but CBD does not directly stimulate CB1 and CB2, the canonical cannabinoid receptors, like THC does. THC, marijuana’s principal psychoactive component, makes a person feel high by binding to CB1, the most abundant protein receptor in the brain and central nervous system.

THC fits snugly into a special pocket -- an “orthosteric” binding site -- on the CB1 receptor. The image of lock-and-key is apropos for orthosteric binding: THC, the molecular key, fits into the CB1 receptor lock and turns it on, which triggers a signaling cascade on a cellular level that inhibits the release of other neurotransmitters (thereby protecting the brain from too much excitation). It’s one of the many reasons why THC is such a remarkable therapeutic substance.

CB1’s orthosteric binding site is also the “keyhole” for THC’s endogenous cousins, anandamide (the first endocannabinoid compound discovered in the mammalian brain) and 2AG (our most abundant endocannabinoid). Likened to the brain’s own marijuana, these endogenous cannabinoid compounds fit into the same orthosteric binding pocket as THC and activate some of the same signaling mechanisms.

New data versus old science

Since the CB1 receptor was discovered in 1988, it’s been an article of faith among cannabinoid researchers that CBD, unlike THC, has little binding affinity for CB1. But this notion is based on old science.

New data emerging from the international cannabinoid research community indicates that CBD interacts directly with the CB1 receptor in ways that are therapeutically relevant. But CBD parks at a different docking site on CB1 that is functionally distinct from THC’s orthosteric binding site. CBD attaches to what’s known as an “allosteric” binding site on the CB1 receptor.

When cannabidiol, an allosteric modulator of CB1, docks at the receptor, it does not initiate a signaling cascade. But it does impact how the CB1 receptor responds to stimulation by THC and the endogenous cannabinoids. Allosteric modulation of CB1 changes the conformation (shape) of the receptor, and this can have a dramatic impact on the efficiency of cell signaling.

Every cell membrane has lots of receptors for many types of messenger molecules, which influence the activity of the cell. It’s not uncommon for a receptor to have two distinct binding sites or loci that can be activated by various drugs and endogenous compounds. The orthosteric site is the switch that a drug turns on, whereas an allosteric modulator can either amplify or decrease a receptor’s ability to transmit a signal depending on how the allosteric modulator changes the conformation of the receptor.

To extend the lock-and-key metaphor: If the orthosteric binding site is the lock on a door, then the allosteric binding site, when activated, makes the lock easier or more difficult to open. A “positive allosteric modulator” changes the shape of the receptor in a way that potentiates receptor signaling, while a “negative allosteric modulator” will reduce receptor transmission.

Healing without the high?

Numerous pharmaceuticals target orthosteric binding sites for receptor stimulation. Big Pharma has also brought to market several synthetic allosteric modulators of other receptor systems (Mimpara, Piracetam, and Selzentry, for example). There is serious interest among drug companies in allosteric modulation of the endocannabinoid system. In theory, if not practice, allosteric modulators can prime the system for amplification or inhibition by fine-tuning receptor transmission with amazing subtlety.

Full-on stimulation of CB1 can deliver therapeutic benefits, but THC’s psychoactivity intrinsically limits its medical utility, according to Big Pharma catechism. For the medical constabularies, getting high is by definition an adverse side effect. Allosteric modulation raises the prospect of increasing CB1 receptor activity without causing disconcerting dysphoria or needless euphoria.

Scientists at the University of Aberdeen in Scotland have synthesized a positive allosteric modulator of CB1 to treat pain and neurological disorders. When researchers at Virginia Commonwealth University tested the compound on mice, this experimental drug, known as “ZCZ011,” had no psychoactive effects of its own, but reduced neuropathic and inflammatory pain by boosting the CB1 receptor’s response to anandamide, an endocannabinoid compound.

Research into allosteric modulation of the endocannabinoid system is still in its early phases. Allosteric modulators of CB1 were first discovered in 2005. Ten years would elapse before scientists at Dalhousie University in Halifax, Canada, reported in the British Journal of Pharmacology that cannabidiol is a negative allosteric modulator of CB1 in vitro. This means that CBD lowers the ceiling on the ability of THC and endogenous cannabinoids to stimulate CB1.

The Canadian research team identified the exact molecular niche where CBD parks at the CB1 receptor, a protein which consists of 472 amino acids strung together in a crumpled chain that wraps around the cell membrane seven times. Scientists can mutate CB1 receptors with precision, targeting one amino acid at a time. Data generated by mutational analysis pinpointed positions 98 and 107 on CB1’s amino acid chain as the key docking loci for CBD.

A Dimmer Switch

Negative allosteric modulation of CB1 is conceptually similar to a dimmer switch on a light fixture. CBD alters cognition and improves mood; it creates mood lighting for the brain and dims the ‘strobe light’ triggering seizures. As a negative allosteric modulator of the CB1 receptor, CBD shows particular promise for treating conditions associated with endocannabinoid excess or overactivity (obesity, metabolic disorders, liver disease, cardiovascular issues), whereas a positive allosteric modulator that enhances CB1 receptor signaling could be helpful for diseases linked to endocannabinoid deficits (such as anorexia, migraines, irritable bowel, fibromyalgia, and PTSD).

It should be noted that allosteric modulators typically are unable to alter receptor conformation unless the orthosteric binding site is also stimulated. CBD can modulate CB1 receptor signaling only when THC or another cannabinoid compound is active at the orthosteric binding site. In terms of whole plant cannabis therapeutics, CBD’s efficacy as an allosteric modulator requires the co-presence of THC.

THC and CBD work in tandem; they are the power couple of cannabis therapeutics. Given the intimate synergies between these two plant compounds, how much sense does it make to attribute psychoactivity exclusively to one (THC) and not the other (CBD)? Is it really accurate to say that CBD is a “non-psychoactive” substance?

Researchers have demonstrated that CBD confers antipsychotic, anxiolytic (anxiety-reducing), and antidepressant effects. If CBD can relieve anxiety or depression or psychosis, then obviously cannabidiol is a profound mood-altering substance, even if it doesn’t deliver much by way of euphoria. Perhaps it would be better to say that CBD is “not psychoactive like THC,” rather than repeating the familiar and somewhat misleading refrain that “CBD is not psychoactive.”

The identification of cannabidiol as a negative allosteric modulator that binds directly to the CB1 receptor challenges antiquated assumptions about CBD and sheds new light on its medicinal potential. In turn, as our scientific understanding and therapeutic experience deepens, the description of CBD as non-psychoactive may fall by the wayside.

Jahan Marcu is Chief Science Officer at Americans for Safe Access with 14 years of experience in Cannabis research and regulations. Ali S. Matthews is the pen name of an endocannabinoid researcher currently studying allosteric modulators and the mammalian brain, who wishes to protect the privacy and identity of his federally funded laboratory. Martin A. Lee is the director of Project CBD and the author of Smoke Signals: A Social History of Marijuana -- Medical, Recreational and Scientific.

Copyright, Project CBD. May not be reprinted without permission.


Abood ME. “Allosteric Modulators: A Side Door.” J Med Chem. 2016 Jan 14;59(1):42-43.

Bogna Ignatowska-Jankowska, et al. “A cannabinoid CB1 receptor positive allosteric modulator reduced neuropathic pain in the mouse with no psychoactive effects.” Neuropsychopharmacology. 2015 July 29.

Elham Khajehli et al. “Biased agonism and biased allosteric modulation at the CB1 receptor.” Molecular Pharmacology. 2015 June 4.

Kukarni PM, et al. “Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s).” J Med Chem. 2015 Nov 3.

Laprairie RB, et al. “Cannabidiol is a negative allosteric modulator of the type 1 cannabinoid receptor.” Br J Pharmacol. 2015 Jul 27.

Straiker A, et al. “Aiming for allosterism: Evaluation of allosteric modulators of CB1 in a neuronal model.” Pharmacological Research 2015 Jul 23.

Kevin McKernan: Sequencing the Cannabis Genome

kevin mckernan cannabis genome
By on January 05, 2016

Kevin McKernan on sequencing the cannabis genome and its implications for the cannabis industry and “personalized medicine.”


Project CBD: We’re speaking with Kevin McKernan, chief scientific officer of Medicinal Genomics, a Massachusetts-based company which a few years ago—I believe in 2011—sequenced the cannabis genome or a particular cannabis strain.

McKernan: Yes, that’s right.

Project CBD: This would seem to have some significant implications for the cannabis industry as a whole. We’d like to explore that with you. Maybe you could explain a little bit about what we mean by “sequencing the cannabis genome”?

McKernan: Sure. So, this was in 2011 and the tools we had to sequence back then were still evolving very, very quickly, but we were able to get a very draft version of this genome sequence. Now what this is, is reading every letter in the genome and really, in any cannabis samples, many know there are two genomes: there’s really the mother and father genome. The plant is known to be diploid. So it’s got 20 chromosomes and one copy of each from mother and father, there are some chloroplasts and mitochondria genome in there as well, but we want to read all of those letters so we can begin to build a map of all of the genetics that might predict cannabinoid expression, terpene expression, maybe even flavonoid expression. As it moves into hemp, maybe some of the genes that are governing either seed size and oil and fiber.

So to read the entire genome, it’s about 1 billion bases long, it’s a billion letters of genetic code. In the process, with the technology we have, we probably only got about 400-500 megabases of really nicely aligned sequence. Now that seems like it, you’ve only gotten about half of the genome. That’s probably true. There’s a lot of repetitive nature in plant genomes. They have copies of things that are identical scattered throughout them. And those end up when you sequence them, it’s kind of like putting together a big jigsaw puzzle. Those are like all the pieces that look the same. And sometimes you don’t know exactly where they go. And so they get—they’re in the sequence but they get kind of left as ambiguous when you put all this data together. But we do have is a really nice scaffolds of some of the genes everyone is very attentive to, like THC synthase is one that is of real interest, really nice sequence coverage of those, CBDA synthase and some of the genes that are governing cannabinoids.

Project CBD: When you say “synthase” you’re talking about the kind of the precursor gene for what will become CBD or the gene that encodes the enzyme that creates CBDA and THCA?

McKernan: Yeah, so it’s an enzyme involved that the DNA codes for protein, and that protein folds into little enzymes that folds the precursor molecule into either THC—and there’s another gene called CBDA synthase, and the “A” is for the acid form because it makes THCA and CBDA before it, in the plant form. That’s taking a Cannabigerol precursor, and if you look at Cannabigerol, it’s like a ring structure and it’s got a long tail on it that it kinds of folds and wraps into two more cyclical groups that either makes THC, or one more cyclical group can make CBD. And there’s two different genes responsible for folding that precursor two different ways, and they’re actually in competition for the precursor.

So we believe, and many others before us have actually done this work to demonstrate that DNA variants in those genes have some predictive capacity on how much THC it’s going to make. So, there’s been some publications showing mutations in key areas of the gene—and this is known as a FADA-binding domain, a very technical term for a really catalytic core of the enzyme, that folds those molecules. And when there’s DNA variance in there, it does a slower job at it. Sometimes it doesn’t do any job at it. So, we believe—this is kind of a [rheostat] of how much THC is produced depending on where these variants are in the gene. And if we can get a better picture of this, we can begin to predict these chemotypes of the plant at a seedling stage without having to fully grow them out.

Now, the environment is always going to play a role in this dance as well, but we’re just trying to get a really firm picture of the genetics so that we can have some understanding of the capacity of the plant. If we know the plant is going to make all CBD, you might put that in a different grow room, or you might do something different with it, breed it with something else where you’re trying to bring CBD in. But if you know it’s going to be really strong THC strain that perhaps gives you a different direction to go with it.

Project CBD: You’ve touched on some of the implications of this genetic science for cultivators, for breeders possibly, or for people who are trying to fine-tune particular strains for particular medicinal properties. Let’s get into this a little bit more. How will this really be—this kind of knowledge—other than pure science, how will it be applicable for growers or for the cannabis industry as a whole?

McKernan: So, where we’ve seen this take foothold in other marketplaces is with a process known as “marker assisted selection.” I’m a much bigger fan of that type of breeding than let’s say let’s go monkey around with the genes, when we don’t really understand the whole genome yet. So the genome stuff, I think, is a little bit arrogant right now, and maybe even ever, depending on how much we ever get to know about this genome. But what people do tend to do with the sequence information in breeding is they use the DNA markers to track the traits. And it’s just kind of a measuring tool. Instead of measuring the chemotypes as they grow out—which is a great way, I don’t think that’s ever going to go away. But if you want to measure what chemotypes you might get at the first sign of the leaf, there’s information to be had there that can tell you, okay, here’s the terpene profile we think it’s going to have.  

Now we don’t know the markers that do that today, but this is what they’ve done in other very valuable crops, is that they get an understanding of maybe 100,000 to a million of these different single letter changes in the genomes, and they track those in all the plants. And they use those as sort of a proxy for, okay all of these changes over here tend to track with terpinolene and these ones tend to track with beta-caryophyllene , and these ones tend to track with maybe pinene. And so, we know that those markers are predictive that this plant’s going to be, maybe a myrcene dominant indica, and this one’s going to be a pinene or something that’s more Jack Herer—like with a terpinolene.

So those markers we think at a hole-punch we could distill. You could get a hole-punch of the leaf, all you need is about 30 nanograms of DNA to do this. This is 30 billionths of a gram of DNA that you could get this information from, and it will give you maybe 100,000 to 1 million different data points on the strain. Ultimately, there’ll be databases to help you correlate that all right, this pattern is from a plant that’s on this part of the phylogenic tree and we know that it tends to make these types of terpenes. And we’re going to track those SNIPS, they’re called single-nucleotide polymorphism. So there’s a lingo here what people call them SNIPS. Once we have that, we can then make some more informed decisions about, okay, we have a wonderful plant over here making some cannabigerol and some cannabichromene and we really want to bring in limonene to this, and what do we cross it with to make that happen in the fastest way possible. So we think it becomes just a tool set to help guide breeding. And this process called “marker assisted selection” is simply a fancy term for we’re going to measure this with something other than photography to perhaps guide where we go with the breeding.

Project CBD: So Medicinal Genomics has actually been gene sequencing several different strains, many different samples?

McKernan: We have, yes.

Project CBD: And what have you found in terms of diversity or lack thereof, and how has prohibition affected that?

McKernan: So it’s a fascinating question. There’s certainly signs of there being a genetic bottleneck toward high-THC plants. But at the same time of that having happening, there’s been a tremendous amount of inter-breeding that’s going on, that if you were to compare the variation we might see in the drug type plants, next to those that we see in the plants that have had less prohibition on them, like hemp plants (hemp plants are registered and there’s process in some countries to actually legally grow those), you actually see far more genetic diversity in the drug types, the ones that are underground. And, although they might have more THC in them, there has been perhaps a lot more exchange to find different terpenes or to breed different traits into them. I’ve always found that very fascinating: that the ones that are a little bit more above board and leveraging perhaps the registries and the patent systems actually have less genetic diversity then what we’re finding in the markets that perhaps that are out here.

Project CBD: Let’s talk a little bit about the implications for the medical use of marijuana. Personalized medicine is a buzzword today within the cannabis therapeutics world, and in terms of what that means, I think, on the ground for patients—patients are sort of groping in the dark to find what strain might work best for them, what helps them the most, maybe what ratio of CBD to THC is going to be their entry point into utilizing cannabis medicinally, and that always comes down to well, it’s about that person, how that person is going to relate to a particular strain or the plant in general. But I think what you’re talking about with the science of genetics sort of takes this idea of personalized medicine to a whole different level. So, how—and I know also that Courtagen, your sister company, has been working on the human side of the genome—so how do the two come together and what does this mean for personalizing medicinal cannabis?

McKernan: So I’m really excited about this topic because we—on the flip side of our business we’re sequencing 700-800 patients a month to try and find variants that help dosing patients with different drugs; sometimes it does implicate that you might benefit if you go straight to CBD. The classic case is sodium channel 1 mutations or Dravet syndrome, and they are the class of patients that are responding very well—not just anecdotally on the Internet, but even in the FDA-based trials you can’t deny this, that they’re having a real positive affect from [GW Pharmaceuticals’s] Epidiolex, that they’re testing this on.

Project CBD: You’re speaking about CBD or CBD-rich product, it’s helping these particular children with epilepsy and in terms of Dravets, but there are many different epileptic diseases 

McKernan: We tend to sequence 500 genes for epilepsy patients because it’s a long-tail, and this is really the lesson of personalized medicine. It’s kind of a lesson of the FDA, is that they’re not designed for personalized medicine. They’re designed for one-size-fits-all drugs, that aspirin and things just hit everybody with the same thing. Those are gone. There are no more of those. There are very few of them. And it’s pretty clear now that the reason drugs are failing in the FDA and the reason the costs are going up is that they’re trying to apply this model of blockbuster drugs to shove it through the FDA. What we’re really seeing in cancer and all these fields is that everyone’s genome is, we differ by probably 4 million variants in our own genome. And so what you might describe as chronic pain could be a completely different molecular mechanism if I have chronic pain. And we begin to understand that when we dive in and sequence people’s genomes. Oh yeah, you have chronic pain because you have TRP receptors that are off. And I have chronic pain because I have a TRAP1 variant. And those might require different mechanisms for dosing. It might require different cannabinoids.

And so, I’m very excited about bringing those two fields together because we can see the personalized medicine—there’s only one market in the country that I think has grown faster than personalized medicine, and it’s cannabis. And cannabis is this market that has, what looks to be, about to become, the largest open source set of pharmaceutical drugs that grow to high concentrations in plants that are weeds. I mean this is a total revolution in medicine that’s about to become over-the-counter for physicians; that if we can line up the right patient variants with the right cannabinoid and terpene profiles, the cost of health care is just going to go right down. And we can do—what I would like to call it as, it’s almost like a technological leapfrogging event, right. You see these cases where two different technologies kind of—the two different tsumanis that are coming together and they create a kind of a perfect storm of a wave.

Project CBD: The two different technologies are now the—?

McKernan: I think it’s the personalized medicine insight. Knowing the patient’s genome and then also knowing the entire cannbinoid profile of these plants—and the reason I’m fairly focused and myopic on the cannabinoids is because it’s really not that myopic at all! There’s just a whole portfolio of these things, and they all grow in the best factory you can imagine. There’s certainly a lot of interest in ripping these genes out and putting them into yeast and seeing if you can keep up with the plant.

Project CBD: That’s not your focus.

McKernan: No, I think that’s harder. I think it’s a harder job to do. And the plant’s very good and it grows—we have all this infrastructure to grow this plant. What you do find, in some places the pharmaceutical industry, they want to put their pathways into plants like this because they become medicinal factories for them. And then, you know, we have a science of growing this plant that’s quite mature and produces tons of this stuff. So, I’m actually quite optimistic about that side of the equation being done just perfectly today. But to bring the two together, you do see these destructions happen in other markets that I’m always very attentive to, that you see things like new batteries that are coming out these days can now drive things on the ground that are gyroscopic scooters now, and cars like Tesla, and then there’s solar panel technologies—and when those things come together, you see third world’s skipping landlines right now. They’re not installing landlines, they’re going right to Nokia cellphones. They’re not going to build central banks because they have cryptocurrencies or M-Pesa like currencies that are happening in Kenya.

The same thing I think is going to happen in medicine with the FDA. The FDA is one form of doing medicine, but it can’t scale with the innovation that’s out there. And the innovation I see really happening in medicine is, at this level, is the level of trying to get cannabinoids to the right patients. And that model is much more democratized, it’s much more individualistic, it’s much more focused on and respectful of each patient being unique. And we’re losing that in the health care system. The health care system is getting very one-size-fits-all.

Project CBD: In a sense what you’re talking about, is kind of eliminating the “crap shoot.” If you’ve got a drug, and you have a person with a certain genetic constitution, and you’re throwing CBD at an epileptic kid, why does it stick with some kids, why does it work so amazingly and why doesn’t it work with others? So you would be able to determine this in advance?

McKernan: We’re starting to see some signals on this. And this isn’t any coordinated effort, necessarily, with FDA or with GW [Pharmaceuticals]. Because we sequence so many patients at Courtagen, we happen to have a lot of patients that are in those trials, and they tell us. And when we take their data and compare the responders to the non-responders, we can see that there’s a pattern. They’re starting to show a pattern of the responders have variants, there are four particular variants that we’ve been showcasing that they have. And interestingly enough, they’re in—one’s in a drug metabolism gene known as a CYP2C9 gene, it’s a gene involved in the metabolism of CBD. The other three genes that are showing some predictive power here are sodium channel genes that we know anandamide interacts with. So there’s a thesis here that kind of makes sense. And the reason it’s important is, in some of those patients, CBD isn’t their molecule. They get 2-400 percent, smaller, 15 percent of the kids get worse. When seizure patients, like Dravet patients get worse, it’s extensively worse. It’s like they get intubated. They end up in the ER. Sometimes they get Status Epilepticus. And often times you hear anecdotally, some of those parents switch into THC or THCA, and they get better.

So there’s different mechanisms of causing seizures, and I think as we understand those mechanisms from a genetic level, we get more challenging about which cannabinoids to hand them. We don’t know the answer to how to mix and match that perfectly today. That’s kind of the vision. That’s where we want to go. But I think what we’re going to see over time is that puzzle is going to slowly fill in piece by piece, publication by publication, that these variants, very predictive of success and this class of patients. This class of patients really needs maybe a THCA, which is a completely different molecular pathway.

Project CBD: It’s very exciting. Presumably that could be applicable to other conditions, and not just the epilepsy.

McKernan: I think so. I think chronic pain is one. We’ve published a paper on the chronic pain front. And some of these patients were very responsive to antioxidants. And we all know that some of the best lipid soluble antioxidants in the world are cannabinoids. So these patients didn’t happen to jump on that. But the fact that they were responsive to N-acetyl cysteine, which is more of a—not as much as a lipid soluble antioxidant, so it could be some improvement there. It’s very exciting to us because this variant is in 1-2 percent of the population. It’s in a gene known as TRAP1, that has some implications in cancer, but it’s never really been pinned to chronic pain or chronic fatigue. And so, we refer about 1,000 patients and we summed up all the patients that had chronic pain and chronic fatigue and Bang! A big signal pops out saying TRAP1. And when that gene’s broken the hypothesis is it’s making lots of reactive oxygen species [ROS]. So your body is churning through energy and creating all the side products of energy consumption, but it’s not actually functional. And that’s creating, we think, the pain and the fatigue, it’s that this enzyme is broken, it’s eating up all the ATP [adenosine triphosphate].

So we’re really hopeful that that will translate into maybe making a dent into this opiate problem, right. These people are just getting handed opiates and it’s probably not really addressing the core issue of creating lots of ROS, it’s just dulling the pain that’s coming from. And we’ve seen where that’s gone. It’s just gone into total and complete opiate epidemic right now.

So, we’re hopeful that some of the sequencing will come in and objectify what is the subjective problem for a physician. Patient shows up and says I have pain. Sure you do. Then they have to really monitor how much dosage they give them and whether it becomes chronic, whether they get GI issues with the opiates. But if you had a molecular marker that said no, these are the patients that actually have a broken gene that we know responds with antioxidants, you can suddenly change that conversation to “we should be considering cannabinoids for this.” I’m hopeful that’s going to happen in autism, in mitochondrial disease. We’ll probably see it in Parkinson’s and Alzheimer’s. A whole host of diseases that you can see on the Project CBD website that are playing a role. And they probably all have different molecular mechanisms as to how CBD is benefiting those things.

Project CBD: Well I think Medicinal Genomics is changing the conversation. And that’s great. It’s amazing the work that you’re doing. I appreciate Kevin McKernan for being with us today.

McKernan: Thank you. We’re excited about the field.

Copyright, Project CBD. May not be reprinted without permission.

Audio-visual category: 

How Safe is Your Vape Pen?

cbd vape oil
By on July 14, 2015

The Hidden Dangers of Propylene Glycol

Jahan Marcu, PhD, reports on the hidden dangers of propylene glycol and vape pens that smolder.

Portable electronic devices, known as “vape pens,” are increasingly popular among medical marijuana patients and others because they provide a convenient, discreet, and presumably benign way to administer cannabis. But how safe are vape pens and the liquid solutions inside the cartridges that attach to these devices? Who knows what’s actually being inhaled?

It’s generally assumed that vaping is a healthier method of administration than inhaling marijuana smoke, which contains noxious substances that may irritate the lungs. Since a vaporizer heats the cannabis flower or oil concentrate without burning it, the active ingredients are inhaled but no smoke is involved. At least that’s how it’s supposed to work.

But there may be a hidden downside to vape pens, which are manufactured (typically in China), marketed, and utilized without regulatory controls. Available online and in medical marijuana dispensaries, vape pens contain a battery-operated heating mechanism, which at high temperatures can transform solvents, flavoring agents, and various vape oil additives into carcinogens and other dangerous toxins.

Of particular concern: Propylene glycol, a widely used chemical that is mixed with cannabis or hemp oil in many vape pen cartridges. A syrupy, thinning compound, propylene glycol is also the primary ingredient in a majority of nicotine-infused e-cigarette solutions. At high temperatures, propylene glycol converts into tiny polymers that can wreak havoc on lung tissue.

Scientists know a great deal about propylene glycol. It is found in a plethora of common household items—cosmetics, baby wipes, pharmaceuticals, pet food, antifreeze, etc. The U.S. Food and Drug Administration and Health Canada have deemed propylene glycol safe for human ingestion and topical application. But exposure by inhalation is another matter. Many things are safe to eat but dangerous to breathe.

A 2010 study published in the International Journal of Environmental Research and Public Health concluded that airborne propylene glycol circulating indoors can induce or exacerbate asthma, eczema, and many allergic symptoms. Children were said to be particularly sensitive to these airborne toxins. An earlier toxicology review warned that propylene glycol, ubiquitous in hairsprays, could be harmful because aerosol particles lodge deep in the lungs and are not respirable.

When propylene glycol is heated by a red-hot metal coil, the potential harm from inhalation exposure increases. High voltage heat can transform propylene glycol and other vaping additives into carbonyls. Carbonyls are a group of cancer-causing chemicals that includes formaldehyde, which has been linked to spontaneous abortions and low birth weight. A known thermal breakdown product of propylene glycol, formaldehyde is an International Agency for Research on Cancer group 1 carcinogen.

Because of low oral toxicity, propylene glycol is classified by the FDA as “generally recognized as safe” (GRAS) for use as a food additive, but this assessment was based on toxicity studies that did not involve heating and breathing propylene glycol.

Prevalent in nicotine e-cig products and present in some vape oil cartridges, FDA-approved flavoring agents pose additional risks when inhaled rather than eaten. The flavoring compounds smooth and creamy (diacetyl and acetyl propionyl) are associated with respiratory illness when inhaled in tobacco e-cigarette devices. Another hazardous-when-inhaled-but-safe-to-eat flavoring compound is cinnamon ceylon, which becomes cytotoxic when aerosolized.

Currently, there is no conclusive evidence that frequent users will develop cancer or another illness if they inhale the contents of vape oil cartridges. That’s because little is actually known about the short or long-term health effects of inhaling propylene glycol and other ingredients that are present in flavored vape pen cartridges. Many of these prefilled cartridges are poorly labeled with little or no meaningful information on their contents.

The possibility that vape pens might expose people to unknown health hazards underscores the importance of adequate safety testing for these products, which thus far has been lacking.

Scientists face several challenges as they try to gather relevant safety data. As yet, no one has determined how much e-cig vapor the typical user breathes in, so different studies assume different amounts of vapor as their standard, making it difficult to compare results. Tracing what happens to the vapor once it is inhaled is equally problematic.

The biggest variable is the device itself. The performance of each vape pen can vary greatly between different devices and sometimes there is considerable variance when comparing two devices of the same model.

Some vape pens require pressing a button to charge the heating coil; others are buttonless and one activates the battery simply by sucking on the pen. The surface area of the vape pen’s heating element and its electrical resistance play a large role in converting ingestible solvents into inhalable toxins.

Another confounding factor is the scant information on when and how long the user pushes the button or inhales on average, how long the coil heats up, or the voltage used during the heating process. A five-volt setting yielded higher levels of formaldehyde in a controlled propylene glycol study cited in the New England Journal of Medicine.

In the case of vape pens, there’s a great need for specific research on how people actually use these products in the real world in order to understand potential benefits or harms.

Such studies have been conducted using the Volcano vaporizer, a first generation vaping device that differs from a vape pen, a more recent innovation, in several ways. Utilized in clinical trials as a medical delivery device, the Volcano is not a portable contraption. The Volcano only heats raw cannabis flower, not oil extract solutions, and it doesn’t combust the bud.

Vape pen manufacturers don’t like to admit it, but when the heating element gets red hot in a vape pen, the solution inside the prefilled cartridges undergoes a process called “smoldering,” a technical term for what is tantamount to “burning.” While much of the vape oil liquid is vaporized and atomized, a portion of the vape oil blend undergoes pyrolysis or combustion. In that sense, most of the vape pens that have flooded the commercial market may not be true vaporizers.

Unlike vape pen devices, the Volcano vaporizer has been tested for safety and pharmacokinetics (a measurement of what’s in the blood and how long it stays there). Collectively, the data indicate that vaporizing whole plant cannabis exposes the user to lower amounts of carcinogens compared to smoke and decreases side effects (such as reactions to the harshness of smoke).

But nonportable vaporizers like the Volcano may still pose health concerns if the vaporized cannabis flower is below acceptable botanical safety standards. A recent article in the Journal of Analytical Methods notes that high levels of ammonia are produced from vaporizing cannabis grown incorrectly, perhaps due to the lack of flushing during hydroponic cultivation. There’s a growing body of data suggesting that the chemicals used to push the plant towards unnaturally high THC concentrations stay in the finished product.

Dr. Jahan Marcu is the chief scientist for Americans for Safe Access (ASA) and chief auditor for ASA's Patient Focused Certification program. He serves on the board of various trade association and science organization committees, including the American Chemical Society, the International Association for Cannabis as Medicine, and the American Herbal Products Association.

CBD Hemp Oil Vape Cartridges with Propylene Glycol

Project CBD research associate Eric Geisterfer conducted a limited survey of cannabis vape oil and CBD hemp vape oil cartridges. Several of these products were found to include propylene glycol as an additive. The list below is incomplete—vape oil products are continually being introduced and in some cases rebranded.

Hemp oil vape cartridges that contain Propylene Glycol

  • Alternate Vape
  • Bluebird Botanicals
  • CannaVape CBD Oil
  • Cloud 9 CBD
  • Delta Liquids
  • Entourage Hemp Products also known as Cannoid LLC
  • Hemp Life Today (also known as Cannazall)
  • Hemp Pure Vape
  • Hemp Vap
  • KanaVape
  • Miracle Smoke
  • Michigan Hemp Company (also known as Bluegrass Naturals)
  • Pure CBD Vapors
  • Pure Hemp Vape
  • Tasty Hemp Oil
  • Zamnesia CBD Smart Liquid

Some cannabis vape oil cartridges also include propylene glycol or polyethylene glycol as a thinning agent. Both compounds may have adverse health effects when heated and inhaled. Neither has been safety tested by the FDA for inhalation when heated. Cannabis consumers should carefully scrutinize cannabis product labels.

    Copyright, Project CBD. May not be reprinted without permission.

    Article Sources

    • Boom in E-cigarettes Sparks Debate. Chem Eng News. 2015;93(7):10-13.
    • Abrams DI, Vizoso HP, Shade SB, Jay C. Vaporization as a smokeless cannabis delivery system: a pilot study. Clinical Pharmacology …. 2007. doi:10.1002/(ISSN)1532-6535.
    • Barrington-Trimis JL, Samet JM, McConnell R. Flavorings in Electronic Cigarettes: An Unrecognized Respiratory Health Hazard? JAMA. 2014;312(23):2493-2494. doi:10.1001/jama.2014.14830.
    • Choi H, Schmidbauer N, Sundell J, Hasselgren M, Spengler J, Bornehag C-G. Common Household Chemicals and the Allergy Risks in Pre-School Age Children. Hartl D, ed. PLoS ONE. 2010;5(10):e13423. doi:10.1371/journal.pone.0013423.
    • Choi H, Schmidbauer N, Spengler J, Bornehag C-G. Sources of Propylene Glycol and Glycol Ethers in Air at Home. International Journal of Environmental Research and Public Health 2010, Vol 7, Pages 4213-4237. 2010;7(12):4213-4237. doi:10.3390/ijerph7124213.
    • Etter J-F. Electronic cigarettes and cannabis: an exploratory study. Eur Addict Res. 2015;21(3):124-130. doi:10.1159/000369791.
    • Gieringer D, Laurent JS, Goodrich S. Cannabis Vaporizer Combines Efficient Delivery of THC with Effective Suppression of Pyrolytic Compounds. doi:10.1300/J175v04n01_02.
    • Hazekamp A, Ruhaak R, Zuurman L, van Gerven J, Verpoorte R. Evaluation of a vaporizing device (Volcano®) for the pulmonary administration of tetrahydrocannabinol. J Pharm Sci. 2006;95(6):1308-1317. doi:10.1002/jps.20574.
    • Hazekamp A, Grotenhermen F. Review on clinical studies with cannabis and cannabinoids 2005-2009. Cannabinoids. 2010;5(special):1-21.
    • Jensen RP, Luo W, Pankow JF, Strongin RM, Peyton DH. Hidden Formaldehyde in E-Cigarette Aerosols. N Engl J Med. 2015;372(4):392-394. doi:10.1056/NEJMc1413069.
    • Nitzkin JL, Farsalinos K, Siegel M. More on hidden formaldehyde in e-cigarette aerosols. N Engl J Med. 2015;372(16):1575. doi:10.1056/NEJMc1502242#SA1.
    • Pomahacova B, Van der Kooy F, Verpoorte R. Cannabis smoke condensate III: The cannabinoid content of vaporised Cannabis sativa. Inhalation Toxicology. 2009;00(00):090619130156077–5. doi:10.1080/08958370902748559.
    • Wallace MS, Marcotte TD, Umlauf A, Gouaux B, Atkinson JH. Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy. J Pain. 2015;0(0). doi:10.1016/j.jpain.2015.03.008.

    Prohibition’s Last Gasp: “CBD Only”

    Cannabis Prohibition
    By on March 26, 2015

    "What is falling, we must still push."—Nietzsche

    Industrial hemp oil marketers tried to put a positive spin on the Food and Drug Administration’s recent slap-down of companies that pitch CBD products as legal in all 50 states.

    In late February and early March, the FDA sent warning letters to 11 companies for making unproven medical claims about their CBD-infused products.

    The FDA also tested some of the commodities peddled by these companies and found that in many cases the products contained little or no cannabidiol.

    The FDA warning letters did not address other mislabeling red flags, such as assertions that CBD is extracted from the stalk and seed of the hemp plant, not the leaves and flowers.

    Nor did the FDA directly address CBD’s legal status. CBD hemp oil boosters were heartened because the FDA didn’t say CBD-infused oil per se is illegal.

    But the fact that the FDA sidestepped the issue of CBD’s legality does not necessarily mean that the FDA signed off on it. The FDA has yet to approve CBD either as a dietary supplement or a drug.

    Nutraceutical merchants, meanwhile, are chomping at the bit for CBD. They yearn for clarity regarding the legal status of CBD oil derived from industrial hemp with less than 0.3 percent tetrahydrocannabinol (THC).

    Cannabidiol extracted from CBD-rich cannabis remains illegal under federal law, despite the fact that it is not an inebriant, is nonlethal, and has no known adverse side effects (though drug interactions can be problematic).

    State legislatures aren’t waiting for a signal from the Feds. Thirteen states in recent months have enacted so-called “CBD-only” laws, or better put, “Low THC laws,” though a cynic might call them “Keep marijuana illegal” laws.

    Backed by conservative Republicans and blue dog Democrats who have long opposed medical marijuana, most of these CBD-only bills ostensibly provide an affirmative defense that allow certain people to use cannabidiol-rich oil derived from hemp or cannabis that measures below or near 0.3 percent THC, the federal guideline. But each state government sets its own rules. Some limit the sources of CBD-rich products and specify a narrow range of conditions for which CBD can be used; others do not.

    Will CBD-only laws prove to be a key first step toward full-fledged medical marijuana legislation in Red State America? Or is “CBD-only” a cul-de-sac that delays and thwarts safe access to a broader range of cannabis therapies?

    To date, it is difficult for residents of CBD-only states to obtain CBD-rich oil legally. And even if they could, many would be disappointed to find that low-THC oil doesn’t work for everyone. Most medical marijuana patients are not adequately served by CBD-only laws. They need access to a wide spectrum of whole plant cannabis remedies, not just low THC medicine.

    Parents of children with seizure disorders and other serious illnesses have been at the forefront of lobbying state officials to enact laws to protect families seeking access to CBD-rich oils. In February, politicians in Virginia—where hemp growing was once mandatory by colonial decree—enacted low THC legislation in response to pleas from parents and other patient advocates.

    The Virginia parents had learned through online discussion groups and illicit, hands-on experimentation that augmenting CBD-rich oil by adding some THC—or better yet, THCA, the raw unheated version of THC—helps with seizure control in many instances.

    THCA, like CBD, is a non-psychotropic marijuana compound. If ingested, THCA doesn’t make a person feel “high.” THCA turns into THC, The High Causer, after the dried marijuana flower-tops are “activated” by exposure to heat via combustion or cooking.

    So the Virginia pols “legalized” THCA, as well as CBD, thereby providing an affirmative defense for some patients who need safe access to medicinal cannabis.

    For years, elected officials and government bureaucrats have slandered this plant, demonized it, demeaned it, and denied its therapeutic value. And now, after decades of hyperbolizing the evil weed and trivializing the funny stuff, policymakers are chopping the herb into bits and pieces, legalizing some marijuana molecules while shunning other parts of the still forbidden Schedule I botanical.

    And if all else fails our fearless leaders, who have long since forfeited any claim to credibility with respect to marijuana, have one last trick up their sleeve. They can consign the plant to Schedule II and restrict patient access by needlessly insisting that doctors write prescriptions in triplicate for those who might benefit from cannabis therapeutics.

    Rescheduling cannabis as a Schedule II substance should smooth the way for long-suppressed clinical research. That would be a positive development. Placing cannabis in Schedule II would be a significant advancement in other ways, as well. But Schedule II doesn’t go nearly far enough. Cannabis—high THC, CBD rich, and any variation thereof—should be de-scheduled and regulated as a medicinal herb, not as a single-molecule pharmaceutical or a street drug.

    Copyright, Project CBD. May not be reprinted without permission.

    Single Compound vs. Whole Plant CBD

    Whole plant cannabis versus CBD isolates
    By on February 22, 2015

    A groundbreaking study from Israel has documented the superior therapeutic properties of whole plant CBD-rich cannabis extract as compared to single-molecule cannabidiol (CBD).

    Published in the journal Pharmacology & Pharmacy (Feb. 2015), the article directly challenges one of the sacred cows of Big Pharma and the medical-industrial complex -- the notion that “crude” botanical preparations are inherently low grade and less effective than pure, single-molecule compounds.

    Entitled “Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol,” the article is all the more noteworthy given the contribution of co-author Lumir Hanus, who was instrumental in the discovery of anandamide, the endogenous cannabinoid compound first identified in the mammalian brain in 1992.

    Hanus and two Israeli colleagues from Hebrew University of Jerusalem surveyed the scientific literature and noted that during the past fifteen years numerous preclinical studies had focused on the anti-inflammatory effects of pure, single-molecule CBD in animal models of various pathologies, including rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and diabetes. (See preclinical data regarding CBD.)

    These studies showed that administration of pure, single-molecule CBD resulted in a bell-shaped dose-response curve, meaning that when the amount of CBD exceeded a certain point its therapeutic impact declined dramatically. “Healing was only observed when CBD was given within a very limited dose range, whereas no beneficial effect was achieved at either lower or higher doses,” the authors observed. This characteristic of single-molecule CBD — manifested as a bell-shaped dose response — imposes serious obstacles that limit its usefulness in a clinical context.

    The Israeli team sought to determine whether the administration of a whole plant CBD-rich extract would also generate a bell-shaped dose-response curve when administered to mice. Or would cannabidiol extracted from CBD-rich Cannabis avoid this liability? “The aim of the present study,” the authors explained, “was to find a CBD source that could eliminate the bell-shaped dose-response of purified CBD.”

    The scientists obtained a CBD-rich strain called “Avidekel” from Tikkun Olam, an Israeli medical marijuana producer. Referred to as “clone 202” in this study, Avidekel has hardly any THC and therefore is not intoxicating. The origins of Avidekel can be traced to Spain, where breeders developed several phenotypes of “Cannatonic” (as in “cannabis tonic”), including a strain that measures close to 20 percent CBD by dry weight with almost no intoxicating ingredients. (The same high-yielding CBD-dominant strain is known as “ACDC” in California.)

    The Israeli researchers extracted CBD-rich oil from clone 202. The extract—consisting of 17.9 percent CBD, 1.1 percent THC, 1.1 percent cannabichromene (CBC), 0.2 percent cannabigerol (CBG), and “traces” of cannabinol (CBN) and cannabivarol (CBDV)—was given to mice to evaluate its anti-inflammatory and painkilling effect.

    For comparative purposes, the scientists administered pure CBD to another group of mice and assessed its anti-inflammatory and analgesic properties. They also compared the extent to which single-molecule CBD and whole plant CBD inhibited the production of tumor necrosis factor alpha (TNFa), a systemic inflammatory signaling molecule. Dysregulation of TNF-alpha production has been implicated in several diseases including cancer, Alzheimer’s, clinical depression, and irritable bowel syndrome.

    The pure CBD tests confirmed the findings of earlier preclinical research. Once again, single-molecule CBD administration generated a bell-shaped dose-response curve with a narrow therapeutic window.

    But a different dose response pattern was observed when the clone 202 extract was administered to mice. Rather than showing a bell-shaped curve, where a therapeutic effect could only be achieved at a certain concentration of pure CBD, the whole plant CBD-rich extract caused a direct, dose-dependent inhibition of pain, inflammation, and TNFa production. “In stark contrast to purified CBD,” the Israeli team reported, “the clone extract...provided a clear correlation between the anti-inflammatory and anti-nociceptive responses and the dose, with increasing responses upon increasing doses, which makes this plant medicine ideal for clinical uses.”

    Moreover, the Israeli researchers found that a small amount of CBD in the clone extract was needed for significant pain relief compared to the much larger amount of pure CBD required to achieve the same analgesic effect. And whereas pure, single-molecule CBD precipitated a dramatic drop in efficacy if more than a specific dosage was administered, an “overdose” of whole plant CBD-rich extract did not undermine its therapeutic potency. When greater than an optimal dose of the clone 202 oil was administered, its effectiveness leveled off, suggesting that a medicinal plateau had been reached.

    The Israeli study found that Cannabis clone 202 extract “is superior over CBD for the treatment of inflammatory conditions.” The greater efficiency of the whole plant extract might be explained by additive or synergistic interactions between CBD and dozens of minor phytocannabinoids and hundreds of non-cannabinoid plant compounds. “It is likely that other components in the extract synergize with CBD to achieve the desired anti-inflammatory action that may contribute to overcoming the bell-shaped dose-response of purified CBD,” the Israeli team surmised.

    The scientists also felt it was important to examine how the CBD-rich Cannabis extract compared with commercial painkillers and anti-inflammatory drugs. They found that both pure CBD and the clone 202 extract exhibited greater anti-inflammatory potency than aspirin. Aspirin, but not tramadol, registered a slight inhibitory effect on TNFa production, which was negligible in comparison to the strong inhibitory effect of pure CBD and clone 202.

    The key finding that CBD in the presence of other Cannabis components improves the dose-response is supported by recent reports documenting the anti-proliferative effect of cannabidiol on tumor cells and the inhibitory effect of CBD on bladder contractility.

    “A lot of research has been made to isolate and characterize isolated single constituents of traditional herbal medicine to find their rationale for therapeutic uses,” the Israeli team concluded. “However, our data together with those of others provide legitimation to introduce a new generation of phytopharmaceuticals to treat diseases that have hitherto been treated using synthetic drugs alone. The therapeutic synergy observed with plant extracts results in the requirement for a lower amount of active components, with consequent reduced adverse effects.”

    Copyright, Project CBD. May not be reprinted without permission.

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    CBD Misconceptions

    Cannabis misconceptions, marijuana misinformation
    By on February 18, 2015

    Updated: August 2, 2015

    It doesn’t get you high, but it’s causing quite a buzz among medical scientists and patients. The past year has seen a surge of interest in cannabidiol (CBD), a non-intoxicating cannabis compound with significant therapeutic properties. Numerous commercial start-ups and internet retailers have jumped on the CBD bandwagon, touting CBD derived from industrial hemp as the next big thing, a miracle oil that can shrink tumors, quell seizures, and ease chronic pain—without making people feel “stoned.” But along with a growing awareness of cannabidiol as a potential health aid there has been a proliferation of misconceptions about CBD.

    1. “CBD is medical. THC is recreational.” Project CBD receives many inquiries from around the world and oftentimes people say they are seeking “CBD, the medical part” of the plant, “not THC, the recreational part” that gets you high. Actually, THC, “The High Causer,” has awesome therapeutic properties. Scientists at the Scripps Research Center in San Diego reported that THC inhibits an enzyme implicated in the formation of beta-amyloid plaque, the hallmark of Alzheimer’s-related dementia. The federal government recognizes single-molecule THC (Marinol) as an anti-nausea compound and appetite booster, deeming it a Schedule III drug, a category reserved for medicinal substances with little abuse potential. But whole plant marijuana, the only natural source of THC, continues to be classified as a dangerous Schedule I drug with no medical value.
    2. “THC is the bad cannabinoid. CBD is the good cannabinoid.” The drug warrior’s strategic retreat: Give ground on CBD while continuing to demonize THC. Diehard marijuana prohibitionists are exploiting the good news about CBD to further stigmatize high-THC cannabis, casting tetrahydrocannabinol as the bad cannabinoid, whereas CBD is framed as the good cannabinoid. Why? Because CBD doesn’t make you high like THC does. Project CBD categorically rejects this moralistic, reefer madness dichotomy in favor of whole plant cannabis therapeutics. (Read the foundational science paper: A Tale of Two Cannabinoids.)
    3. “CBD is most effective without THC.” THC and CBD are the power couple of cannabis compounds—they work best together. Scientific studies have established that CBD and THC interact synergistically to enhance each other’s therapeutic effects. British researchers have shown that CBD potentiates THC’s anti-inflammatory properties in an animal model of colitis. Scientists at the California Pacific Medical Center in San Francisco determined that a combination of CBD and THC has a more potent anti-tumoral effect than either compound alone when tested on brain cancer and breast cancer cell lines. And extensive clinical research has demonstrated that CBD combined with THC is more beneficial for neuropathic pain than either compound as a single molecule.
    4. “Single-molecule pharmaceuticals are superior to ‘crude’ whole plant medicinals.” According to the federal government, specific components of the marijuana plant (THC, CBD) have medical value, but the plant itself does not have medical value. Uncle Sam’s single-molecule blinders reflect a cultural and political bias that privileges Big Pharma products. Single-molecule medicine is the predominant corporate way, the FDA-approved way, but it’s not the only way, and it’s not necessarily the optimal way to benefit from cannabis therapeutics. Cannabis contains several hundred compounds, including various flavonoids, aromatic terpenes, and many minor cannabinoids in addition to THC and CBD. Each of these compounds has specific healing attributes, but when combined they create what scientists refer to as a holistic “entourage effect,” so that the therapeutic impact of the whole plant is greater than the sum of its single-molecule parts. The Food and Drug Administration, however, isn’t in the business of approving plants as medicine. (See the scientific evidence.)
    5. “Psychoactivity is inherently an adverse side effect.” According to politically correct drug war catechism, the marijuana high is an unwanted side effect. Big Pharma is keen on synthesizing medically active marijuana-like molecules that don’t make people high—although it’s not obvious why mild euphoric feelings are intrinsically negative for a sick person or a healthy person, for that matter. In ancient Greece, the word euphoria meant “having health,” a state of well-being. The euphoric qualities of cannabis, far from being an unwholesome side effect, are deeply implicated in the therapeutic value of the plant. “We should be thinking of cannabis as a medicine first,” said Dr. Tod Mikuriya, “that happens to have some psychoactive properties, as many medicines do, rather than as an intoxicant that happens to have a few therapeutic properties on the side.”
    6. “CBD is legal in all 50 states.” Purveyors of imported, CBD-infused hemp oil claim it’s legal to market their wares anywhere in the United States as long as the oil contains less than 0.3 percent THC. Actually, it’s not so simple. Federal law prohibits U.S. farmers from growing hemp as a commercial crop, but the sale of imported, low-THC, industrial hemp products is permitted in the United States as long as these products are derived from the seed or stalk of the plant, not from the leaves and flowers. Here’s the catch: Cannabidiol can’t be pressed or extracted from hempseed. CBD can be extracted from the flower, leaves, and, only to a very minor extent, from the stalk of the hemp plant. Hemp oil start-ups lack credibility when they say their CBD comes from hempseed and stalk. Congress may soon vote to exempt industrial hemp and CBD from the definition of marijuana under the Controlled Substances Act. Such legislation would not be necessary if CBD derived from foreign-grown hemp was already legal throughout the United States. (Read more: Sourcing CBD: Marijuana, Industrial Hemp & the Vagaries of Federal Law)
    7. “'CBD-only’ laws adequately serve the patient population.” Fifteen U.S. state legislatures have passed “CBD only” (or, more accurately, “low THC”) laws, and other states are poised to follow suit. Some states restrict the sources of CBD-rich products and specify the diseases for which CBD can be accessed; others do not. Ostensibly these laws allow the use of CBD-infused oil derived from hemp or cannabis that measures less than 0.3 percent THC. But a CBD-rich remedy with little THC doesn’t work for everyone. Parents of epileptic children have found that adding some THC (or THCA, the raw unheated version of THC) helps with seizure control in many instances. For some epileptics, THC-dominant strains are more effective than CBD-rich products. The vast majority of patients are not well served by CBD-only laws. They need access to a broad spectrum of whole plant cannabis remedies, not just the low THC medicine. One size doesn’t fit all with respect to cannabis therapeutics, and neither does one compound or one product or one strain. (Read more: Prohibition’s Last Gasp: “CBD Only.”)
    8. “CBD is CBD—It doesn’t matter where it comes from.” Yes it does matter. The flower-tops and leaves of some industrial hemp strains may be a viable source of CBD (legal issues notwithstanding), but hemp is by no means an optimal source of cannabidiol. Industrial hemp typically contains far less cannabidiol than CBD-rich cannabis. Huge amounts of industrial hemp are required to extract a small amount of CBD, thereby raising the risk of toxic contaminants because hemp is a “bio-accumulator” that draws heavy metals from the soil. Single-molecule CBD synthesized in a lab or extracted and refined from industrial hemp lacks critical medicinal terpenes and secondary cannabinoids found in cannabis strains. These compounds interact with CBD and THC to enhance their therapeutic benefits. (See also: Sourcing CBD: Marijuana, Industrial Hemp & the Vagaries of Federal Law.)

    Copyright, Project CBD. May not be reprinted without permission.

    On The Frontiers Of Hemp Science

    Hemp science
    By on February 16, 2015

    The original name of the ICRS was “International Cannabis Research Society.” In 1995—after the body’s own cannabinoid receptor system had been discovered and elucidated by ICRS members—the group changed the C-word in its name to “Cannabinoid.” As pharmacologist Dale Deutsch explained in 1998, “The field is moving away from the plant.”

    The 2014 ICRS meeting marked the return of the plant to the forefront of the field. Neurologist Ethan Russo was serving as president (the job is held for a year), and he invited the Italian natural product chemist Giovanni Appendino to give the featured talk.

    Appendino, a professor at the Università del Piemonte Orientale, noted proudly that he is from Carmagnola, a northern Italian town renowned for its fiber hemp variety of the same name.
    Appendino first published research in the cannabinoid field in 2002, when he was co-author of a paper on “Noladin ether—a putative endocannabinoid.” The lead authors were Raphael Mechoulam and Vincenzo DiMarzo. But his “relationship with cannabis as fiber hemp” goes much further back, he said. “My grandfather was growing it and the odor of hemp retting tanks filled the air around Carmagnola during the Fall.”

    “Nature has varied on the cannabinoid structure,” Appendino observed. Cannabis researchers have focused almost e. xclusively on THC, CBD, CBC (cannabichromene), and CBG (cannabigerol, precursor to the other three) while not investigating the therapeutic potential of related molecules present in Cannabis — and other plants as well.

    Similarly, by defining cannabinoids as drugs that work at the CB1 and CB2 receptors (the canonical cannabinoid receptors concentrated in the central and peripheral nervous system, respectively), researchers may be overlooking beneficial compounds in Cannabis that work by other mechanisms.

    In the course of screening more than 200 varieties of fiber hemp, Appendino and colleagues have found significant quantities of obscure compounds whose medical potential he considers “worthy of investigation.”

    He touched briefly on canniprene, the cannflavins, cannabinoid esters, and “sesqui-CBG,” which Appendino’s group isolated from a fiber hemp variety.

    Appendino has encountered a hemp variety containing two percent canniprene—a compound he called “the Cannabis version of resveratrol” (a beneficial antioxidant compound present in red grapes).

    From others varieties of hemp he isolated the prenylated version of cannbigerol—meaning CBG with a prenyl group attached. Prenylation entails the addition of a hydrophobic molecule to a protein or chemical compound, which may facilitate lipid binding to cell membranes.

    There is no reason, Appendino said, that marijuana should not also produce the prenylated version of THC—which would have distinct biological activity.

    Cannabinoids not unique to Cannabis

    Cannabinoids are not unique to cannabis—they have been found in other plants. Appendino reported that a large amount of CBG and its carboxylic precursor (CBGA) had been isolated from a specific Helichrysum variety found only in South Africa.

    Studying how Helichrysum makes “non-cannabis” CBG and its related compounds has been difficult for Appendino and his colleagues, because strict South African bio-piracy laws prohibit the collection and export of native species or their seeds. These laws, designed to prevent foreign corporate exploitation of the country’s unique genetic resources, also impede legitimate scientific research. After two years of bureaucratic red tape, Appendino was only able to obtain a small vial of extract from Helichrysum, and has not been able to obtain seeds of the plant to continue his research.

    Appendino discovered that cannabinoid-like compounds are made by plants “apart from the normal cannabinoid biosynthetic route. There is a new pathway that starts from an aromatic acid.” Referred to as the “Helichrysum cannabinoids,” these compounds also have been detected in liverwort, a diuretic herb helpful for bronchitis and liver congestion, as well as gallbladder, kidney, and bladder problems.

    Helichrysum is used in African ethno-pharmacology, Appendino explains, “like hemp, to make fumes in ritual ceremonies” and that a “psychotropic effect...similar to cannabinoids,” might ensue.


    Appendino also discussed some of the therapeutic attributes of terpenoids, the largest class of naturally occurring compounds on the planet. Terpenoids, or terpenes, are the chemicals that give plants their unique smells and flavors. Found in high concentrations in many culinary herbs and spices, terpenes not only provide flavor and scent, they are also important signaling chemicals that plants use to communicate with insects.

    Some plants up-regulate specific terpenes when attacked by herbivores to render the plant less palatable to the attacking insect. In a beautiful demonstration of the web that Mother Nature has created, these same terpenes have been shown to recruit parasitic bugs that themselves attack the herbivores which are eating the plant!

    Present in black pepper, bitter leafy greens, Echinacea, and many cannabis strains, beta-caryophyllene is one of the terpenes that plants use to defend themselves against predators.

    Terpenes are synthesized by the plant from five-carbon isoprene units, two of which come together in specialized cellular compartments to form the 10-carbon monoterpenes (limonene, pinene, linalool, terpinolene, et al). The 15-carbon sesquiterpenes, such as β-caryophyllene, differ from the monoterpenes by the incorporation of an extra isoprene unit. (β is the Greek letter beta.)

    Monoterpenes are more volatile at lower temperatures, so when Cannabis is dried, stored for periods of time, or made into extracts, the monoterpenes are generally first to evaporate while the sesquiterpenes like β-caryophyllene are more likely to remain.

    Appendino recounted how the wild, ancestral relative of corn, teosinte, grown by the Mayan and Incan farmers in pre-European Central and South America, produced significant amounts of β-caryophyllene before modern breeders selected towards high yielding corn with an increased sugar content. The drive to breed high-yielding varieties of corn for intensive commercial agriculture sacrificed the ability of the plant to produce β-caryophyllene .

    At the 2007 ICRS meeting, Jürg Gertsch reported that β-caryophyllene binds specifically to the CB2 cannabinoid receptor, which regulates immune function and is found mainly outside the central nervous system.

    Big Pharma has taken note of CB2’s role as an immune cell modulator. But the CB2 receptor has yet to be successfully exploited by the pharmaceutical industry, observed Appendino in 2014: “If drug discovery is a sea, then CB2 is a rock that is surrounded by shipwrecked-projects,” he commented poetically.

    Pharmaceutical companies have spent large sums investigating proprietary synthetic CB2-selective compounds that end up showing little clinical efficacy. “But β-caryophyllene is a special lottery ticket,” said Appendino.

    β-caryophyllene seems like the Cannabis plant’s own perfect key for nature’s CB2 lock. Appendino described how the β-caryophyllene molecule interacts with the CB2 receptor. It’s an unusual physical relationship for cannabinoid-type agonists. β-caryophyllene does not look like any other molecule that binds to the cannabinoid receptors.

    Known to be anti-inflammatory and easy on the stomach lining, plant extracts high in β-caryophyllene have produced analgesic and anti-inflammatory effects in clinical trials. “Maybe the interaction of β-caryophyllene with CB2 is an echo of an ancient dialog between plants and insects,” Appendino mused.

    Expanded-Definition Cannabinoids (EDCs)

    Just as natural selection tinkers with compounds, so do scientists, hoping to find a useful modification that evolutionary pressure hasn’t induced nature to come up with. Research is underway into some of the unorthodox cannabinoids Appendino discussed.

    Appendino’s expanded concept of cannabinoid drugs involves an expanded concept of the endocannabinoid system. In addition to CB1 and CB2, the biological targets of the EDCs include the GPR55 receptor; transcription factors in the mitochondria that switch genes on and off; and TRP (pronounced “trip”) receptors, which function as ion channels with gates that open and close to transmit signals. CBD, CBG, and other phytocannabinoids bind to various TRP receptors.

    A Spanish biotech company called VivaCell has developed a drug, VCE-003, in which a quinol group has been attached to CBG.  VCE-003 outperforms CBG in activating PPAR receptors, which are situated on the cell’s nucleus and regulate gene expression and metabolic function. VCE-003 has shown efficacy in studies using mouse models of Multiple Sclerosis and Encephalomyelitis.

    Drugs like VCE-003 are known as “semi-synthetics.” Hydrocodone and buprenorphine, which have replaced codeine and morphine and most opioid analgesics now sold in the U.S., are well-known semi-synthetics.

    The process by which a semi-synthetic drug is created can be patented, whereas a natural product cannot be patented. This raises the question of whether such drugs are in fact superior for medical reasons or for commercial purposes.

    Cannabis & Cancer

    CBD, cannabis and cancer
    By on February 15, 2015

    Published in full in Freedom Leaf Magazine.

    Synergy: The interaction of elements that when combined produce a total effect that is greater than the sum of the individual elements, contributions, etc.

    Millions of Americans now have access to medical marijuana. When it comes to cancer treatment, the plant may have an amazing impact when used in concert with traditional therapies. Beyond helping with the nausea of chemotherapy, there is strong scientific evidence of a deeper benefit of using cannabis with conventional therapies. Cancer cells can become extremeley sensitive to THC and CBD after being exposed to radition or chemotherapy.

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    All Vape Pen Oils Are Not Created Equal

    AbsoluteXtracts vape cartridges
    By on December 05, 2014

    Published in full on

    A Quick and Easy User’s Guide to Pre-Filled Cartridges

    Vaporizer pens are all the rage these days. Sarah Silverman flashed one on the red carpet (“This is my liquid pot,” she quipped). Whoopi Goldberg wrote a gushy love letter to hers, affectionately nicknaming it “Sippy.” Snoop Dogg has his own proprietary model, which comes cloaked in a map of his old Long Beach ‘hood. The Oxford English Dictionary recently crowned “vape” its Word of the Year.

    It seems that everywhere you turn someone is sucking on a sleek, sexy, subversive little wand. People are vaping cannabis oil on the street, in restaurants, movie theaters, airplanes, even sporting events. You feel like you’re getting away with something sneaky when you vape in public. Being a stoner has never been so easy.

    A vape pen—or “personal vaporizer,” as they are sometimes called—is a classy, high tech gizmo that heats cannabis oil to a temperature just short of combustion, releasing a smokeless, lightly-scented mist free of toxic tars and carbon. There are many vape pen brands, but the key factor, really, is what’s inside the disposable cartridge. How potent is the cannabis oil? How pure? What, if anything, is the oil cut with? How expensive per milligram is the THC content? Is the oil strain-specific or a psychoactive blend?

    O’Shaughnessy’s looked at a total of 19 cannabis oil samples from 13 popular cartridge brands and did a side-by-side comparison based on analytical data from SC Labs in Santa Cruz. (Measured in milligrams per milliliter of concentrate, the data is posted on Regarding THC levels, Pure Cure and AbsoluteXtracts topped the chart at 71 percent and 70 percent, respectively. Neither is cut with an additive. AbsoluteXtracts features a line of strain-specific oils (OG Kush, Chem Dawg, Girl Scout Cookie, etc.), while Pure Cure is presumably a mixture of several unnamed cultivars as no strain designation is indicated. These two brands also rated highest in terms of bang for buck with AbsoluteXtracts priced at 10 cents per milligram of THC and Pure Cure at 11 cents/mg.

    Compare those numbers to O-Pen Vape Panama Sativa Red, for example, which contains only 26 percent THC at cost of 24 cents per milligram. Some vape pen cartridge oils rated even lower in terms of THC content, yet higher in price per milligram. The least potent sample, BD (Black Diamond) Vape Sour D, tested at 14 percent THC, while selling for 28 cents/mg of THC. Although they look golden and pretty, the weaker oils are typically diluted with propylene glycol, a relatively benign solvent that sometimes causes sore throat and dry mouth. Avoid vape pen cartridges that include ethylene glycol, an unhealthy compound used in antifreeze.

    So buyer beware: Many vape cartridge brands are available in the unregulated cannabis market and it’s not always obvious what you’re getting. Deciding between vape cartridges is somewhat like choosing between a vintage scotch and a flask of moonshine, though in this case purchasing one of best whiskeys of the cartridge world might actually leave you with a few more greenbacks in your pocket.

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